The objective of this research proposal is to determine the effect of dietary selenium supplementation on mammary carcinogenesis induced in rats by 7,12-dimethylbenz(a)anthracene (DMBA) with special emphasis on the ability of selenium to reduce the marked tumor incidence observed in rats fed a high fat diet. Our interest in selenium as a potential anticarcinogen stems primarily from its ability to protect against peroxidation. The lability of a given tissue to oxidative damage is a function of the balance between the concentration of polyunsaturated lipids and the antioxidant defense capacity. Thus uncontrolled lipid peroxidation may occur as a result of a high unsaturated fat intake and in the absence of an adequate supply of intracellular antioxidant. In this study, we will look into the effect of selenium status on the susceptibility of the mammary tissue to carcinogenesis and the lability of the tissue to lipid peroxidation in rats fed a high fat versus a low fat diet and in rats fed a saturated fat versus an unsaturated fat diet. We are also interested in finding out whether additional vitamin E and methionine can enhance the efficacy of selenium in this regard, since these two compounds are known to potentiate the antioxidant status of the animal. In order to delineate if the action of selenium is distinct from other artificial antioxidants such as butylated hydroxytoluene (BHT), we will determine if the effects of selenium and BHT are additive in the inhibition of DMBA-induced mammary tumorigenesis. By supplementing the diet with selenium either before and after DMBA administration, we will also try to determine if selenium has any influence on DMBA metabolism. If we can conclusively demonstrate that low doses of selenium are effective in inhibiting the development of neoplastic diseases that are promoted by dietary fat, the use of selenium at nutritional levels can offer a potential means of cancer prevention.